A Self-Supervised Image Registration Approach for Measuring Local Response Patterns in Metastatic Ovarian Cancer

High-grade serous ovarian carcinoma (HGSOC) is characterised by significant spatial and temporal heterogeneity, typically manifesting at an advanced metastatic stage. A major challenge in treating advanced HGSOC is effectively monitoring localised change in tumour burden across multiple sites during neoadjuvant chemotherapy (NACT) and predicting long-term pathological response and overall patient survival. In this work, we propose a self-supervised deformable image registration algorithm that utilises a general-purpose image encoder for image feature extraction to co-register contrast-enhanced computerised tomography scan images acquired before and after neoadjuvant chemotherapy. This approach addresses challenges posed by highly complex tumour deformations and longitudinal lesion matching during treatment. Localised tumour changes are calculated using the Jacobian determinant maps of the registration deformation at multiple disease sites and their macroscopic areas, including hypo-dense (i.e., cystic/necrotic), hyper-dense (i.e., calcified), and intermediate density (i.e., soft tissue) portions. A series of experiments is conducted to understand the role of a general-purpose image encoder and its application in quantifying change in tumour burden during neoadjuvant chemotherapy in HGSOC. This work is the first to demonstrate the feasibility of a self-supervised image registration approach in quantifying NACT-induced localised tumour changes across the whole disease burden of patients with complex multi-site HGSOC, which could be used as a potential marker for ovarian cancer patient's long-term pathological response and survival.

Calibrating Ensembles for Scalable Uncertainty Quantification in Deep Learning-based Medical Segmentation

Uncertainty quantification in automated image analysis is highly desired in many applications. Typically, machine learning models in classification or segmentation are only developed to provide binary answers; however, quantifying the uncertainty of the models can play a critical role for example in active learning or machine human interaction. Uncertainty quantification is especially difficult when using deep learning-based models, which are the state-of-the-art in many imaging applications. The current uncertainty quantification approaches do not scale well in high-dimensional real-world problems. Scalable solutions often rely on classical techniques, such as dropout, during inference or training ensembles of identical models with different random seeds to obtain a posterior distribution. In this paper, we show that these approaches fail to approximate the classification probability. On the contrary, we propose a scalable and intuitive framework to calibrate ensembles of deep learning models to produce uncertainty quantification measurements that approximate the classification probability. On unseen test data, we demonstrate improved calibration, sensitivity (in two out of three cases) and precision when being compared with the standard approaches. We further motivate the usage of our method in active learning, creating pseudo-labels to learn from unlabeled images and human-machine collaboration.

Classification of datasets with imputed missing values: does imputation quality matter?

Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete, imputed, samples. The focus of the machine learning researcher is then to optimise the downstream classification performance. In this study, we highlight that it is imperative to consider the quality of the imputation. We demonstrate how the commonly used measures for assessing quality are flawed and propose a new class of discrepancy scores which focus on how well the method recreates the overall distribution of the data. To conclude, we highlight the compromised interpretability of classifier models trained using poorly imputed data.

Advancing COVID-19 Diagnosis with Privacy-Preserving Collaboration in Artificial Intelligence

Artificial intelligence (AI) provides a promising substitution for streamlining COVID-19 diagnoses. However, concerns surrounding security and trustworthiness impede the collection of large-scale representative medical data, posing a considerable challenge for training a well-generalised model in clinical practices. To address this, we launch the Unified CT-COVID AI Diagnostic Initiative (UCADI), where the AI model can be distributedly trained and independently executed at each host institution under a federated learning framework (FL) without data sharing. Here we show that our FL model outperformed all the local models by a large yield (test sensitivity /specificity in China: 0.973/0.951, in the UK: 0.730/0.942), achieving comparable performance with a panel of professional radiologists. We further evaluated the model on the hold-out (collected from another two hospitals leaving out the FL) and heterogeneous (acquired with contrast materials) data, provided visual explanations for decisions made by the model, and analysed the trade-offs between the model performance and the communication costs in the federated training process. Our study is based on 9,573 chest computed tomography scans (CTs) from 3,336 patients collected from 23 hospitals located in China and the UK. Collectively, our work advanced the prospects of utilising federated learning for privacy-preserving AI in digital health.

Focal Attention Networks: optimising attention for biomedical image segmentation

In recent years, there has been increasing interest to incorporate attention into deep learning architectures for biomedical image segmentation. The modular design of attention mechanisms enables flexible integration into convolutional neural network architectures, such as the U-Net. Whether attention is appropriate to use, what type of attention to use, and where in the network to incorporate attention modules, are all important considerations that are currently overlooked. In this paper, we investigate the role of the Focal parameter in modulating attention, revealing a link between attention in loss functions and networks. By incorporating a Focal distance penalty term, we extend the Unified Focal loss framework to include boundary-based losses. Furthermore, we develop a simple and interpretable, dataset and model-specific heuristic to integrate the Focal parameter into the Squeeze-and-Excitation block and Attention Gate, achieving optimal performance with fewer number of attention modules on three well-validated biomedical imaging datasets, suggesting judicious use of attention modules results in better performance and efficiency.

Incorporating Boundary Uncertainty into loss functions for biomedical image segmentation

Manual segmentation is used as the gold-standard for evaluating neural networks on automated image segmentation tasks. Due to considerable heterogeneity in shapes, colours and textures, demarcating object boundaries is particularly difficult in biomedical images, resulting in significant inter and intra-rater variability. Approaches, such as soft labelling and distance penalty term, apply a global transformation to the ground truth, redefining the loss function with respect to uncertainty. However, global operations are computationally expensive, and neither approach accurately reflects the uncertainty underlying manual annotation. In this paper, we propose the Boundary Uncertainty, which uses morphological operations to restrict soft labelling to object boundaries, providing an appropriate representation of uncertainty in ground truth labels, and may be adapted to enable robust model training where systematic manual segmentation errors are present. We incorporate Boundary Uncertainty with the Dice loss, achieving consistently improved performance across three well-validated biomedical imaging datasets compared to soft labelling and distance-weighted penalty. Boundary Uncertainty not only more accurately reflects the segmentation process, but it is also efficient, robust to segmentation errors and exhibits better generalisation.

Calibrating the Dice loss to handle neural network overconfidence for biomedical image segmentation

The Dice similarity coefficient (DSC) is both a widely used metric and loss function for biomedical image segmentation due to its robustness to class imbalance. However, it is well known that the DSC loss is poorly calibrated, resulting in overconfident predictions that cannot be usefully interpreted in biomedical and clinical practice. Performance is often the only metric used to evaluate segmentations produced by deep neural networks, and calibration is often neglected. However, calibration is important for translation into biomedical and clinical practice, providing crucial contextual information to model predictions for interpretation by scientists and clinicians. In this study, we identify poor calibration as an emerging challenge of deep learning based biomedical image segmentation. We provide a simple yet effective extension of the DSC loss, named the DSC++ loss, that selectively modulates the penalty associated with overconfident, incorrect predictions. As a standalone loss function, the DSC++ loss achieves significantly improved calibration over the conventional DSC loss across five well-validated open-source biomedical imaging datasets. Similarly, we observe significantly improved when integrating the DSC++ loss into four DSC-based loss functions. Finally, we use softmax thresholding to illustrate that well calibrated outputs enable tailoring of precision-recall bias, an important post-processing technique to adapt the model predictions to suit the biomedical or clinical task. The DSC++ loss overcomes the major limitation of the DSC, providing a suitable loss function for training deep learning segmentation models for use in biomedical and clinical practice.

Advances in Artificial Intelligence to Reduce Polyp Miss Rates during Colonoscopy

BACKGROUND AND CONTEXT: Artificial intelligence has the potential to aid gastroenterologists by reducing polyp miss detection rates during colonoscopy screening for colorectal cancer. NEW FINDINGS: We introduce a new deep neural network architecture, the Focus U-Net, which achieves state-of-the-art performance for polyp segmentation across five public datasets containing images of polyps obtained during colonoscopy. LIMITATIONS: The model has been validated on images taken during colonoscopy but requires validation on live video data to ensure generalisability. IMPACT: Once validated on live video data, our polyp segmentation algorithm could be integrated into colonoscopy practice and assist gastroenterologists by reducing the number of polyps missed

A Mixed Focal Loss Function for Handling Class Imbalanced Medical Image Segmentation

Automatic segmentation methods are an important advancement in medical imaging analysis. Machine learning techniques, and deep neural networks in particular, are the state-of-the-art for most automated medical image segmentation tasks, ranging from the subcellular to the level of organ systems. Issues with class imbalance pose a significant challenge irrespective of scale, with organs, and especially with tumours, often occupying a considerably smaller volume relative to the background. Loss functions used in the training of segmentation algorithms differ in their robustness to class imbalance, with cross entropy-based losses being more affected than Dice-based losses. In this work, we first experiment with seven different Dice-based and cross entropy-based loss functions on the publicly available Kidney Tumour Segmentation 2019 (KiTS19) Computed Tomography dataset, and then further evaluate the top three performing loss functions on the Brain Tumour Segmentation 2020 (BraTS20) Magnetic Resonance Imaging dataset. Motivated by the results of our study, we propose a Mixed Focal loss function, a new compound loss function derived from modified variants of the Focal loss and Focal Dice loss functions. We demonstrate that our proposed loss function is associated with a better recall-precision balance, significantly outperforming the other loss functions in both binary and multi-class image segmentation. Importantly, the proposed Mixed Focal loss function is robust to significant class imbalance. Furthermore, we showed the benefit of using compound losses over their component losses, and the improvement provided by the focal variants over other variants.

Machine learning for COVID-19 detection and prognostication using chest radiographs and CT scans: a systematic methodological review

Background: Machine learning methods offer great potential for fast and accurate detection and prognostication of COVID-19 from standard-of-care chest radiographs (CXR) and computed tomography (CT) images. In this systematic review we critically evaluate the machine learning methodologies employed in the rapidly growing literature. Methods: In this systematic review we reviewed EMBASE via OVID, MEDLINE via PubMed, bioRxiv, medRxiv and arXiv for published papers and preprints uploaded from Jan 1, 2020 to June 24, 2020. Studies which consider machine learning models for the diagnosis or prognosis of COVID-19 from CXR or CT images were included. A methodology quality review of each paper was performed against established benchmarks to ensure the review focusses only on high-quality reproducible papers. This study is registered with PROSPERO [CRD42020188887]. Interpretation: Our review finds that none of the developed models discussed are of potential clinical use due to methodological flaws and underlying biases. This is a major weakness, given the urgency with which validated COVID-19 models are needed. Typically, we find that the documentation of a model's development is not sufficient to make the results reproducible and therefore of 168 candidate papers only 29 are deemed to be reproducible and subsequently considered in this review. We therefore encourage authors to use established machine learning checklists to ensure sufficient documentation is made available, and to follow the PROBAST (prediction model risk of bias assessment tool) framework to determine the underlying biases in their model development process and to mitigate these where possible. This is key to safe clinical implementation which is urgently needed.